Tributylphosphine → 4-((5-Chloropyridin-2-yl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203032Notes

Reaction equation

HRID 2203032 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([CH:16]4[CH2:18][CH:17]4[C:19]([OH:22])([CH3:21])[CH3:20])[N:13]([CH3:23])[C:12]=3[CH:24]=2)[C:4](=[O:25])[CH:3]=1.[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:33]O)=[N:31][CH:32]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>CCOC(C)=O.C1COCC1>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:33][O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[CH:10][C:11]4[N:15]=[C:14]([CH:16]5[CH2:18][CH:17]5[C:19]([OH:22])([CH3:20])[CH3:21])[N:13]([CH3:23])[C:12]=4[CH:24]=3)[C:4](=[O:25])[CH:3]=2)=[N:31][CH:32]=1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 20537893(5-Chloropyridin-2-yl)methanolHCID 1213862594-Hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

Product 1

HCID 897024424-((5-Chloropyridin-2-yl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-oneYield 49.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 4-hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (100 mg), (5-chloropyridin-2-yl)methanol (85 mg), tributylphosphine (0.219 ml) and THF (10 ml) was added 1,1′-(azodicarbonyl)dipiperidine (223 mg), and the mixture was stirred at 60° C. for 2 h. The reaction mixture was diluted with EtOAc, quenched with water, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, filtered through silica pad, and concentrated in vacuo. The residue was purified by column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by recrystallization from IPA-IPE to give the title compound (68.4 mg) as an off-white solid.

Workup

  1. customquenched with water
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with water and brine successively
  5. dry with materialdried over MgSO4
  6. filtrationfiltered through silica pad
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (hexane/EtOAc
  9. customEtOAc/MeOH), followed by recrystallization from IPA-IPE

Sources & evidence

ORD record
ord-e39174d601204d0987dd6c273eb42974
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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